This study elucidated the molecular mechanisms underlying chronic spontaneous urticaria (CSU), potentially induced by the food and environmental pollutant dioctyl terephthalate (DOTP), through the application of network toxicology and molecular dynamics simulations. The structural analysis of DOTP was conducted in PubChem, with target prediction executed via Swiss Target Prediction and SuperPred, and target identification standardized using UniProt. A PPI network analysis identified core disease-related targets using STRING and Cytoscape. GO and KEGG analyses were utilized to explore target functions, particularly in inflammation and immune response pathways. AutoDock was employed for molecular docking to predict DOTP's binding to core targets, followed by molecular dynamics simulations with Gromacs to observe detailed interactions and conformational changes in the target proteins. The study identified 38 potential targets associated with CSU and highlighted six core targets-EGFR, BCL2, NFKB1, CASP3, ERBB2, and mTOR-through PPI network analysis. GO and KEGG analyses illuminated the roles of these targets in biological processes, cellular components, molecular functions, and signaling pathways, with a particular emphasis on the PI3K-Akt signaling pathway. Molecular docking demonstrated strong binding affinities between DOTP and the core targets, while molecular dynamics simulations confirmed the stable binding of DOTP to these targets, with exceptional stability observed in its interaction with the mTOR protein. This study clarifies the potential molecular mechanisms of DOTP-induced CSU and underscores the efficacy of network toxicology, molecular docking, and molecular dynamics simulations in assessing the toxicity of food and environmental pollutants and their related molecular biological mechanisms. These findings offer new insights for future research, enhance our comprehension of the potential health impacts of food and environmental pollutants, and establish a scientific foundation for the development of prevention and treatment strategies.

Colorectal cancer is a prevalent malignant tumor with a complex and diverse pathogenesis. In recent years, natural products have shown promising application prospects as sources of anticancer drugs. BBR, a class of benzoquinoline alkaloids extracted from various plants, is widely used in disease treatments owing to its pharmacological activities, including antibacterial, anti-inflammatory, antioxidant, anticancer, and anti-angiogenesis properties. Research has demonstrated that BBR exerts an anti-Salmonella and -Escherichia coli infection effect, attenuating inflammatory reactions by inhibiting harmful bacteria. During the stage of colorectal precancerous lesions, BBR inhibits the activity of cell cyclin by regulating the PI3K/AKT, MAPK, and Wnt signaling pathways, thereby decelerating the cell cycle progression of polyp or adenoma cells. Moreover, the inhibitory effect of BBR on colorectal cancer primarily occurs through the regulation of the cancer cell cycle, anti-angiogenesis, gut microbiota, and antioxidant pathways. The specific involved pathways include the MPK/ERK, NF-kB, and EGFR signaling pathways, encompassing the regulation of Bcl-2 family proteins, vascular endothelial growth factor, and superoxide dismutase. This study reviews and summarizes, for the first time, the specific mechanisms of action of BBR in the carcinogenesis process of colorectal cancer, providing novel insights for its clinical application in intestinal diseases.

Background: Urticaria is a prevalent allergic skin condition that significantly affects patients’ quality of life and mental health. The incidence and prevalence of urticaria vary across regions and time due to globalization and environmental changes. Understanding the global prevalence and impact of urticaria is essential for developing effective prevention and treatment strategies. Objective: To assess the global burden of urticaria and project future trends, with a focus on its incidence, prevalence, and impact on public health. Methods: Utilizing data from the Global Burden of Disease 2021 database, this study assessed urticaria’s incidence, prevalence, mortality, and disability-adjusted life years from 1990 to 2021. Data were analyzed by gender, age, and sociodemographic index. Joinpoint analysis was employed to evaluate global and regional trend changes, while ARIMA and ES models projected the burden to 2050. Results: Between 1990 and 2021, global urticaria incident cases rose 37.9% (84.87 to 117.01 million) and prevalent cases 39.4% (47.95 to 66.84 million). Age-standardized rates remained nearly stable (incidence: 1529.24 to 1533.71/100 000; prevalence: 865.85 to 868.18/100 000; EAPC: 0.01% for both). Central and Eastern Europe had the highest burden. Children <5 years showed the highest incidence (3262.05/100 000). Burden was consistently higher in women. Projections to 2050 indicate a further ~25% increase in cases, driven primarily by demographics. Conclusions: Urticaria’s global burden is expected to rise, influenced by environmental changes, socioeconomic factors, and aging populations. Public health strategies should focus on environmental management, health education, resource optimization, and international cooperation to mitigate urticaria’s impact.

The gut-skin axis represents a critical but poorly understood pathway in atopic dermatitis (AD) pathogenesis. This study aimed to establish causal relationships between gut microbiota and AD risk while identifying key molecular bridges and therapeutic targets. We integrated multiple analytical approaches, including single-cell RNA sequencing analysis of skin biopsies from five AD patients and four healthy controls, intercellular communication network analysis, pseudotime trajectory inference, reverse drug prediction, molecular docking, and molecular dynamics simulations. Analysis revealed increased keratinocyte heterogeneity and enhanced immune cell communication in atopic dermatitis (AD) samples. Intersection analysis between gut microbial metabolite-associated genes and skin pathology-related genes identified seven key bridging genes ( AKR1C2 , GALE , GGH , NR4A1 , PLA2G4B , TYMS ). Functional annotation indicated that these genes are primarily involved in vitamin precursor metabolism, suggesting that the Eubacterium eligens group influences AD pathogenesis mainly through vitamin precursor-mediated pathways that regulate systemic immune responses. Pseudotime trajectory analysis demonstrated dynamic temporal gene expression patterns during disease progression. Molecular docking revealed an unexpectedly high-affinity binding between methotrexate and GALE (binding energy = −10.4 kcal/mol), which exceeded its binding affinity for the classical target TYMS (−7.5 kcal/mol). Molecular dynamics simulations further confirmed the stable binding conformation of the protein-ligand complexes. This study provides mechanistic insights into how the Eubacterium eligens group influences atopic dermatitis through vitamin precursor-mediated systemic immune modulation and identifies GALE as a novel therapeutic target. The findings provide mechanistic insights into the gut-skin axis and support developing precision medicine approaches integrating microbiome interventions with targeted pharmacotherapy for AD management. IMPORTANCE: Genetic-level evidence of gut microbiota causality in atopic dermatitis: this study established a causal relationship between specific gut microbiota and the risk of atopic dermatitis at the genetic level, providing strong genetic evidence for the “gut-skin axis” theory. GALE is identified as a novel therapeutic target with redefined methotrexate mechanism: molecular docking study unexpectedly found that GALE binding affinity of MTX was significantly higher than that of its classical target TYMS, suggesting that GALE may be an important but previously unrecognized target of MTX in the treatment of AD. Multi-omics integration framework reveals increased keratinocyte heterogeneity: integrating single-cell RNA sequencing and computational pharmacology provided a cellular and molecular basis for understanding the characteristics of chronicity and recurrence of the disease.

Background: Endothelial activation is a recognized histological feature of atopic dermatitis (AD), but its transcriptional programs remain incompletely characterized. Methods: We reanalyzed public single-cell RNA-seq data from the skin of five patients with AD and four healthy donors using AD-associated gene set scoring, CellChat, endothelial hdWGCNA and pseudotime ordering, and examined candidate genes with eight machine learning classifiers and SHAP in public bulk transcriptomes of lesional and non-lesional AD skin. Results: Inferred intercellular interactions were more numerous in AD (1348 vs. 1111), with COLLAGEN, CD99 and MIF showing the largest gains in communication strength. Differences in AD-associated gene set scores between AD and healthy endothelial cells were small and inconsistent between scoring approaches. Among seven endothelial modules, Endo7, an NF-κB-responsive immediate-early module containing SELE, ICAM1, IRF1 and NFKBIA, overlapped most strongly with the AD gene set (10 genes; approximately 30-fold enrichment). AD endothelial cells were concentrated at intermediate pseudotime positions (Cohen’s d = 0.334). In bulk skin, classifiers based on 14 LASSO-selected genes separated lesional from non-lesional AD skin in a small test set (AUC 0.70–0.98; likely optimistic estimates, as feature selection preceded the training–test split and paired samples from the same patients may span both partitions), with SELE, TOP2A and IRF1 ranked highest by SHAP. Conclusions: This hypothesis-generating analysis identifies AD-associated endothelial activation signatures and candidate genes that require confirmation in independent, clinically characterized cohorts and experimental studies.